Identifying potential risk genes for clear cell renal cell carcinoma with deep reinforcement learning.

Journal: Nature communications
PMID:

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most prevalent type of renal cell carcinoma. However, our understanding of ccRCC risk genes remains limited. This gap in knowledge poses challenges to the effective diagnosis and treatment of ccRCC. To address this problem, we propose a deep reinforcement learning-based computational approach named RL-GenRisk to identify ccRCC risk genes. Distinct from traditional supervised models, RL-GenRisk frames the identification of ccRCC risk genes as a Markov Decision Process, combining the graph convolutional network and Deep Q-Network for risk gene identification. Moreover, a well-designed data-driven reward is proposed for mitigating the limitation of scant known risk genes. The evaluation demonstrates that RL-GenRisk outperforms existing methods in ccRCC risk gene identification. Additionally, RL-GenRisk identifies eight potential ccRCC risk genes. We successfully validated epidermal growth factor receptor (EGFR) and piccolo presynaptic cytomatrix protein (PCLO), corroborated through independent datasets and biological experimentation. This approach may also be used for other diseases in the future.

Authors

  • Dazhi Lu
    AI for Science Interdisciplinary Research Center, School of Computer Science, Northwestern Polytechnical University, Xi'an, China.
  • Yan Zheng
    School of Computer Science, Northwestern Polytechnical University, West Youyi Road 127, Xi'an, 710072, China.
  • Xianyanling Yi
    Department of Urology, Institute of Urology, West China Hospital.
  • Jianye Hao
    College of Intelligence and Computing, Tianjin University, Peiyang Park Campus: No.135 Yaguan Road, Haihe Education Park, Tianjin, 300350, China. haojianye@gmail.com.
  • Xi Zeng
  • Lu Han
    Pfizer Worldwide Chemical Research and Development, Pfizer Inc. Groton Connecticut 06340 USA Sebastien.Monfette@pfizer.com.
  • Zhigang Li
    Hefei Institute of Physical Science, Chinese Academy of Sciences Hefei 230036 PR China liuyong@aiofm.ac.cn zhanglong@aiofm.ac.cn wangchongwen1987@126.com.
  • Shaoqing Jiao
    Key Laboratory of Symbolic Computation and Knowledge Engineering, Ministry of Education, College of Computer Science and Technology, Jilin University, Changchun 130012, China.
  • Bei Jiang
    Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China.
  • Jianzhong Ai
    Department of Urology, Institute of Urology, West China Hospital.
  • Jiajie Peng
    School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China. jiajiepeng@hit.edu.cn.